In adults, about one-third of patients with nephrotic syndrome will have a systemic disease such as diabetes mellitus, amyloidosis, or systemic lupus erythematosus. The remainder will be categorized as having idiopathic nephrotic syndrome due to one of four forms of glomerular diseases: minimal change, focal glomerular sclerosis, membranous nephropathy, or membranoproliferative glomerulonephritis.
A. Symptoms and Signs: Regardless of the cause, peripheral edema is the hallmark of nephrotic syndrome, though it is not evident until the plasma albumin concentration falls below 3 g/dL. Ascites and anasarca generally develop as a consequence of the severity of the hypoalbuminemia. Exertional dyspnea suggests pulmonary edema associated with severe hypoalbuminemia, large pleural effusions, or restriction of the diaphragm by ascitic fluid. Many patients complain of feeling bloated or "tight" as a result of edema or will complain of abdominal fullness if ascites is present. When secondary to a systemic disease, additional manifestations pertinent to those processes are also present.
1. Urine protein–The screening test to determine if abnormal amounts of protein (specifically, albumin) are being excreted in the urine is the urinary protein dipstick analysis. The dipstick can detect as little as 10–15 mg/dL of protein, but the results must be interpreted in light of the urine specific gravity: A 1+ result in a concentrated specimen (eg, specific gravity 1.030) may have no significance, while a 1+ finding in urine with a low specific gravity (eg, 1.002) may indicate significant protein excretion over 24 hours.
2. Microscopic analysis–Glomerular diseases presenting with nephrotic syndrome often have no cellular elements or casts. The finding of hematuria, pyuria, and cellular casts strongly suggests a glomerular disease that also causes the nephritic syndrome, even if heavy proteinuria is also present. Common to all diseases causing nephrotic syndrome is the presence of oval fat bodies in the urine. These degenerating tubular epithelial cells having cholesteryl esters appear under light microscopy as a cell with "grape clusters," and under polarized light these clusters have a "Maltese cross" appearance.
3. Blood chemistries–Characteristic blood chemistries associated with nephrotic syndrome include a decreased serum albumin (< 3 g/dL), a decreased total serum protein (< 6 g/dL), and an elevated serum cholesterol (> 200 mg/dL).
4. Special tests–Other less common tests performed in patients with nephrotic syndrome may include complement levels (C3, C4, CH50), serum and urine electrophoresis, antinuclear antibody (ANA), and hepatitis serology, specifically for hepatitis B antigen. Data obtained from the history and physical examination determine their appropriateness.
5. Renal biopsy–Renal biopsy is the standard procedure for determining in adults the cause of idiopathic nephrotic syndrome in which the presence of a steroid-treatable or steroid-resistant lesion is possible or likely. Empiric therapy with steroids is not usually recommended unless there is a contraindication to renal biopsy. It should be performed in individuals with persistent proteinuria in whom the etiology or the prognosis of the proteinuria is in doubt as long as there are no medical contraindications to the procedure. Nephrotic-range proteinuria, a result of a systemic disease such as diabetes mellitus or amyloidosis, does not necessitate renal biopsy since that degree of proteinuria represents irreversible glomerular damage from the systemic disease process. Each specimen is examined by light microscopy, after immunofluorescence studies, and with the electron microscope. The histologic pattern—ie, the presence or absence of immune complexes and electron-dense deposits—is most helpful in categorizing the renal abnormality and establishing a diagnosis and thus serves as a guide to therapy and prognosis.
A. Protein Loss: Since increased protein intake can have an adverse effect on renal function in some disease processes, moderation of intake by patients with nephrotic syndrome seems reasonable. A protein intake of 0.5–0.6 g/kg/d and the optional addition of an angiotensin-converting enzyme inhibitor will often reduce the amount of proteinuria. However, if the urinary protein loss exceeds 10 g/24 h, individuals may develop negative nitrogen balance and protein malnutrition. For these individuals, additional quantities of dietary protein, equivalent to their daily losses, may be needed.
B. Peripheral Edema and Ascites: Dietary salt restriction is the key to success in managing edema. However, most patients will eventually need the addition of diuretics. Although thiazide diuretics are used for mild edema, loop diuretics are often employed for the more refractory fluid retention associated with pleural effusions and ascites. The addition of a diuretic such as metolazone or a thiazide acting distal to the loop of Henle may potentiate the diuretic activity of the loop diuretic if one is needed.
C. Hyperlipidemia: Hypercholesterolemia and hypertriglyceridemia frequently accompany nephrotic syndrome. Increased hepatic production of lipids has been generally considered responsible for the hyperlipidemia. Dietary management appears to be of limited value, but most patients should be maintained on a low-fat diet, with a weight control and exercise program.